Use of extracts of capraria biflora in the prevention and/or treatment of senile cataracts

ABSTRACT

The invention provides methods for treating and/or preventing the recurrence of a senile cataract, and/or for inhibiting the development of a senile cataract and/or an incipient senile cataract, in a human or animal subject. The invention further provides nutraceutical compositions suited for the same, derived from an extract of the plant  Capraria biflora.  The compositions comprise the extract in a therapeutically sufficient amount for the treatment and/or prophylaxis of a senile cataract in a human and/or animal subject.

REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of prior U.S. Provisional PatentApplication Ser. No. 61/051,080, filed May 7, 2008.

TECHNICAL FIELD

The present invention relates broadly to the field of healthcare, and inparticular, to the field of ophthalmology, which involves the care ofthe eyes and vision. More specifically, this invention relates to novelnon-surgical methods, having both medical and veterinary application,for the prevention and/or treatment of a particular class of cataracts;the invention also relates to herbal formulations that find use in suchmethods, and which were previously unknown for such use.

BACKGROUND OF THE INVENTION

A cataract is a condition in which an opacity develops in thecrystalline lens of an eye or in the ocular envelope; the opacity mayrange from only slight to complete obstruction of the passage of light.The development of a cataract may lead initially to near-sightedness(myopia) in the affected eye (or eyes), and may progress to blindness ifleft untreated. Moreover, untreated cataracts can cause severeinflammation and/or glaucoma, and may even cause dislocation of thelens.

Senile cataracts are an age-related phenomenon, occurring most commonlyin human subjects who are fifty years of age and older, but age-relatedcataracts also occur in the later lives of other animals, includingspecies in other Families of Order Primates, as well as species fromother Orders and Families of Class Mammalia, such as mice and rats(Order Rodentia), dogs (Family Carnidae), cats (Family Felidae), horses(Family Equidae), cows (Family Bovidae) and other higher mammals.Species from other non-mammalian Classes, such as birds (Class Ayes),are also affected by senile cataracts.

Presently, cataract surgery is the only generally accepted treatment forcataracts (senile or otherwise), and for reasons that are self-evident,is performed almost exclusively only in humans. In cataract surgery, theaffected lens is removed (excised) and replaced by a synthetic(generally plastic or silicone) intraocular lens. While this proceduretypically provides human patients with at least 20/40 vision, it is notwithout its drawbacks.

After surgery, the patient's mobility is reduced and his/her activitylevel must be somewhat suppressed for some time. Moreover, aftercataract extraction surgery, some patients require an additionalprocedure to remove cloudiness that may develop within the posteriorcapsule. Glaucoma, retinal detachment, endophthalmitis and bacterialinfection are all possible complications that may result from, andfollow upon, cataract extraction surgery. Furthermore, some humanpatients may not be candidates for cataract extraction surgery, due toeither a pre-existing medical condition or an unwillingness to undergoan ocular surgery, and animals suffering from senile cataracts arerarely candidates for cataract extraction surgery, since unlike humansubjects, in most cases the extracted lens would not be replaced with asynthetic lens implant, so the animal would remain virtually blind inany event, and also due to the relatively high cost of such veterinaryprocedures.

Accordingly, a method by which cataracts could be treated, in bothhumans and animals, by a non-surgical process would be a useful additionto ophthalmic medicine. Yet, despite much study of the cause andtreatment of cataracts, a clinically useful, non-surgical treatment thatretards the development of senile cataracts has thus far eludedresearchers.

It is therefore the principal object of this invention to provide aclinically useful, non-surgical treatment, having virtually no sideeffects or complications, to reduce the symptoms, or to prevent thedevelopment, of senile cataracts in the lens of the eye of a human oranimal.

It is another object of the present invention to provide a clinicallyuseful, non-surgical treatment that will significantly retard the rateof development of senile cataracts, and thereby eliminate the need formany surgical cataract extractions.

It is yet another object of the present invention to provide a plantmedicament having prophylactic and/or therapeutic properties withrespect to the formation and/or progression of senile cataracts in thelens of the eye of a human or an animal.

SUMMARY OF THE INVENTION

The present invention resides in the surprising discovery, determinedthrough preliminary in-vivo experiments described hereinafter, that theuse of an extract of Capraria biflora effectively reduces or eliminatesthe lens opacity that typifies senile cataracts. It has also been foundthat the continued use of Capraria biflora effectively prevents therecurrence of senile cataracts in previously affected eyes, and alsoprevents the occurrence of senile cataracts in eyes at risk fordeveloping such a condition. Methods of treating senile cataracts areprovided, the methods employing an aqueous extract of Capraria biflorato treat a patient in need of treatment for senile cataracts. Anophthalmically stable aqueous solution appropriate for dispensing to theeye, for the prevention and/or treatment of senile cataracts, is alsoprovided.

The aqueous solution of the invention includes an extract of Caprariabiflora in a therapeutically sufficient amount over time so as toprevent or retard the development of a cataract in a human or animalsubject to which the composition is administered. The composition may bea topical preparation or other dosage unit form suitable forinstillation in the human or animal eye topically, systemically, orintraocularly. Topical dosage forms may include liquid eye droppreparations or ointments that may be instilled externally to the eye,or adsorbed into a material such as a soft contact lens or a collagencorneal shield. On the other hand, intraocular administration may takesuch forms as periocular injection or intraocular instillation (forexample, by implantation of an intraocular reservoir).

The methods of the invention include methods for inhibiting orpreventing the development of a senile cataract, or for inhibiting theprogression of an incipient senile cataract, in a human or animalsubject, which methods comprise administering to such a human or animalsubject an aqueous extract of Capraria biflora in a therapeuticallysufficient amount to prevent or retard the development of a senilecataract in such a subject.

In one embodiment of the invention, an extract of Capraria biflora isapplied to the affected eye which treats an existing senile cataract. Inanother embodiment, the continued use of such an extract effectivelyprevents a senile cataract from recurring in the affected eye. In yetanother embodiment of the invention, such an extract is used as aprophylactic treatment to reduce the risk of developing a senilecataract.

In a further embodiment of the invention, such an extract is used inconjunction with ocular surgery, e.g., a patient with a severe senilecataract may first be treated with such an extract to diminish theseverity of the cataract, which is subsequently removed usingconventional ocular surgical techniques. In yet another embodiment ofthe invention, such an extract may be used post-operatively.

These and other objects, aspects, features and advantages of the presentinvention will become more apparent from, and will be understood moreclearly by reference to, the following detailed description of thepresently most preferred embodiment thereof.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The preferred and other embodiments of the present invention will now befurther described. Although the invention will be illustrativelydescribed hereinafter with reference to an herbal nutraceuticalformulation comprising an aqueous extract of a particular plant species,it should be understood that the invention is not limited to aqueousextracts, but extends to formulations (and to methods utilizing them)that are prepared using other available extraction techniques, providedthat each one yields the active components which are present in theplant species and that exhibit the salutary bio-efficacious propertiesof the present invention as disclosed herein.

The present invention resides in the surprising finding that an extractof the plant Capraria biflora can be formulated into compositions thatare useful for preventing the formation of senile cataracts, or fortreating such cataracts, especially by slowing their progression, inanimals, including humans. Capraria biflora is an evergreen shrub thatranges from the southern United States though Central America and theCarribean to Bolivia in South America. The plant, the formal name ofwhich is Capraria biflora L., is a member of the FamilyScrophulariaceae, and is also known variously as Capraria lanceolate,goat weed, wild tea, savadilla, té del pais, thé du pay, ditay paye andbalsaminha. Indigenous groups in South and Central America have used theleaves of Capraria biflora as an analgesic, anti-inflammatory,anti-pyretic, anti-arthritic, as well as for relief of gastrointestinaldisturbances, to treat hemorrhoids and to treat ophthalmia (inflammationof the eye). However, prior to the development of the present invention,no use of any of the tissues of Capraria biflora, or of any extractthereof, to reduce or eliminate the lens opacity that typifies any typeof cataract, has ever been recorded.

A naphthoquinone compound(6,9-dimethyl-3-(4-methyl-3-pentenyl)naphtho[1,8-bc]-pyran-7,8-dione),designated biflorin, has been isolated from the leaves and roots ofCapraria biflora, and this compound has been shown to have someantimicrobial and cytotoxic activity against tumor cells. Othercompounds which have been isolated from the leaves of C. biflora include2,4a,5,8a-tetramethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-ol, and2-isopropyl-5,5-dimethylcyclohex-2-enone. However, research conductedthus far has not revealed whether any of the specific compoundsmentioned in this paragraph is responsible for, contributes to, or evenplays some role in, the bio-efficacious activity exhibited by theinvention as disclosed herein.

In a preliminary in-vivo experiment conducted by applicant, which willbe described in further detail hereinafter, it was discovered that anextract of Capraria biflora was useful in ameliorating the effects ofcataracts in an animal, specifically, a canine. It was initially thoughtthat such an extract would be useful in preventing and/or treating allclasses of cataracts, in humans as well as in other animals, but furtherin-vivo experiments with rats, in which diabetic cataracts had beeninduced, showed that such extracts were not useful in preventing and/ortreating the diabetic cataracts in such rats, indicating that suchextracts probably would probably not be useful in treating diabeticcataracts in other mammals either. Still later in-vivo experiments withhuman patients, also to be described below, showed that such extractswere useful in preventing and/or treating senile cataracts, from whichthe canine patient had undoubtedly suffered as well. Thus, while atpresent this invention finds use in the prevention and/or treatment ofsenile cataracts, further research may reveal that such extracts may beuseful in treating non-senile, non-diabetic cataracts, such assteroid-induced cataracts or cataracts induced by exposure to chemicalsor to radiation.

In a preferred embodiment of the invention, an extract is prepared fromthe leaves of Capraria biflora, as described in further detail below.The extract may be prepared from such leaves in intact form, or theleaves may first be ground or otherwise processed to maximize theefficiency of the extraction process. In alternative embodiments, otherparts of the Capraria biflora plant, including its flowers, roots,stems, stalks, twigs and/or seeds, may be used in preparing the extract,as it is believed that whatever the active components may be, which arepresent in the leaves of the plant and which exhibit the salutaryproperties of the present invention, may be found in the othervegetative and reproductive organs of the plant as well.

In one embodiment of the invention, the extract is prepared by aconventional aqueous extraction method, that is, by mixing the leaves ofCapraria biflora with hot or boiling water. Specifically, the aqueoussolution is prepared as follows: eight (8) leaves of C. biflora are cutinto small pieces and are placed into a 3-ounce cup, and a balanced salt(aqueous sodium chloride) solution, having a temperature in the range of70° C.-120° C., is poured over them. Benzalkonium chloride (also knownas alkyldimethylbenzylammonium chloride) is then added as apreservative, and the solution is allowed to stand for two (2) days in arefrigerator. The leaves are then removed, and the remaining liquid,constituting the aqueous extract, may then be used in accordance withthe invention, although it is expected that the aqueous extract willhave maximum potency immediately after its preparation, and that theeffectiveness of the aqueous extract will diminish over time. If theaqueous extract is to be used directly, for topical instillation intothe eye in liquid form, that is, as eye drops, then the extract solutionshould be shaken prior to use.

Although as set forth above the leaves may be mixed with the waterdirectly, they may alternatively first be placed in a water-permeablebag, so as to facilitate removal of the spent leaves from the extractsolution thereafter.

In other embodiments of the invention, the aqueous extract may beconcentrated by conventional methods before further use is made of it inaccordance with the invention. In still other embodiments, Caprariabiflora or its aqueous extract is extracted with an organic solvent tofurther separate the active components from non-active components. Suchsolvents may include alcohols such as methanol, ethanol or isopropanol,ketones such as acetone or methyl-ethyl ketone, esters such as ethylacetate or butyl acetate, halogenated solvents such as methylenechloride or chloroform or hydrocarbon solvents such as hexane ortoluene. In yet other embodiments, the individual components of theextract may be isolated using conventional chromatographic techniquesupon conventional supports such as silica, alumina, size-exclusion andion-exchange resins. In further embodiments, the individual componentsof the extract may be separated using distillation, crystallizationand/or chemical derivatization. Such techniques are well known to thosehaving skill in the chemical arts.

The nutraceutical compositions of the present invention can beformulated for prophylactic and/or therapeutic administration by variousmethods that are well known in the ophthalmic arts, maintaining requiredsterility and osmolarity. For example, in another embodiment, theaqueous extract, its concentrate or purified components thereof may bemixed with conventional pharmaceutically acceptable excipients designedto increase the stability of the extract, or of its concentrate or itspurified components, so as to facilitate application to the eye, or toprolong the residence of the extract, its concentrate or its purifiedcomponents upon the ocular surface. Such excipients are well known tothose having skill in the ophthalmic arts. The extract, its concentrateor its purified components may be applied in conventionalpharmaceutically acceptable vehicles such as a solution.

As indicated above, topical instillation in the eye is the preferredmethod of administration, most preferably in the form of liquid eyedrops, although in addition to the alternative embodiment mentionedabove of being administered topically combined with an ophthalmicointment or lubricant, the aqueous extract, its concentrate or purifiedcomponents thereof can also alternatively be administered by beingadsorbed into a soft contact lens (e.g., that marketed by Johnson &Johnson under the trade name “Accuvue Advance”) or a dissolvablecollagen corneal shield.

The nutracuetical compositions of the present invention canalternatively be administered either systemically or by intraocularmeans, although at present these administration routes are lesspreferred. Regarding systemic administration, that is, oral orparenteral administration, the aqueous extract, its concentrate orpurified components thereof may be incorporated into tablets, pills,capsules, etc., wherein the extract, its concentrate or purifiedcomponents thereof is/are dispersed in one or more pharmaceuticallyacceptable, preferably biodegradable, carriers, and wherein the deliverysystem may also include one or more of the following: binders,excipients, lubricants, glidants and/or sweetening agents.

Regarding intraocular administration, that is, direct infusion into theeyeball, the aqueous extract, its concentrate or purified componentsthereof can be administered via injection, or by other delivery routesknown in the ophthalmic arts that are applicable to administer a drug tothe eye. These administration routes can be advantageous when directtreatment of the ocular lens, or the provision of a continuous supply ofthe aqueous extract, its concentrate or purified components thereof tothe eye may be required. However, as it is expected that discontinuoustreatment over time will be the most effective form of therapy, andsince, at least for human patients, a non-invasive administration methodthat also admits of self-administration may be preferable, preparationswhich can be administered topically, particularly as liquid eye dropsusing a conventional eye dropper, are most preferred.

When administered in that form, as a non-concentrated aqueous extract ofCapraria biflora which has not been further purified or furtherextracted with any organic solvents, the preferred dosage is one drop(equivalent to 50 μl) in each affected eye, three times per day, overthe course of four to six weeks. It has been found that for such adosage regimen, the aqueous extract should be replaced with afreshly-prepared aliquot at least once every two weeks, and that anyremaining unused extract in the previous aliquot should not be used. Itis also preferable that each aliquot of the aqueous extract be keptrefrigerated when not in use.

The following working examples illustrate both the manner in which suchan aqueous extract of Capraria biflora in accordance with the presentinvention has been used in both human and animal subjects suffering fromat least one senile cataract, and the experimental results obtained,which demonstrate the efficacy of the invention.

EXAMPLE 1

An elderly male animal, specifically a canine of the dachshund breed,aged 16 years, was observed as having chronically irritated, red eyeswhich made him visibly uncomfortable, and also as having greatlyimpaired vision due to cataracts. The impairment of his vision wasdeduced empirically from his behavior: the subject was observed bumpinginto walls and being unable to find his toys, as well as being unable tofind his food, except by using his sense of smell. An ophthalmologicexamination of the animal confirmed the presence of very dense cataractsin both eyes.

An aqueous extract of C. biflora was prepared and was placed in an eyedropper; this extract was prepared in accordance with the invention,except that only five leaves of C. biflora were used, no preservativewas added, and instead of cooling the extract by refrigeration, it wasallowed to stand at room temperature until it cooled.

One drop was administered to each eye of the canine subject, three timesper day, for about one week at a time, which resulted in a reduction inthe observed eye redness and eye irritation, as well as an increase inthe subject's comfort with his eyes. The administration of the extractwas interrupted on several occasions, upon which the irritation in thesubject's eyes returned within one or two days, but when theadministration of the extract was thereafter resumed, the irritation wasobserved to decrease once again.

After administration of the extract continued without interruption forthree weeks, it was observed that the canine subject's vision hadimproved as well. This was deduced empirically from the animal'sbehavior: he ceased bumping into walls, found his toys and his food moreeasily, and could navigate generally without any observed visualimpairment, from which it was concluded that the administration of theextract had reduced the cataracts from which the animal had suffered.

EXAMPLE 2

A 78-year old Caucasian female with a 20/60 senile cataract in the righteye and a 20/30 senile cataract in the left eye underwent a fullophthalmological examination, which revealed no pathology in either eyeexcept for the cataracts. A picture was taken of the right eye at thistime.

An aqueous extract of C. biflora was prepared in accordance with theinvention, was placed in an eye dropper, and was given to the patient,who thereafter self-administered one drop three times a day, seven daysa week, for three weeks, without missing a single dose, but only in theright eye. The patient was given, and thereafter used, afreshly-prepared aliquot of the aqueous extract once per week, and eachaliquot was kept refrigerated when not in use.

Another ophthalmological examination was conducted three weeks after thefirst administration of the extract. The vision in the right eye hadimproved to 20/30, and upon visual inspection the cataract appearednoticeably clearer. The remainder of the ophthalmological examinationwas within normal limits. Another picture of the cataract in the righteye was taken at this time for purposes of comparison.

The patient reported that she “could see again” and could perform all ofher normal daily activities. Administration of the extract was thereforediscontinued.

EXAMPLE 3

An 81-year old Caucasian female, who had 20/60-vision in both eyes dueto senile cataracts, underwent a full ophthalmological examination andno pathology was found in either eye except for the cataracts. Pictureswere taken of both cataracts at this time.

An aqueous extract of C. biflora was prepared in accordance with theinvention, was placed in an eye dropper, and was given to the patient,who thereafter self-administered one drop in each eye three times a day,seven days a week, for four weeks, without missing a single dose. Thepatient was given, and thereafter used, a freshly-prepared aliquot ofthe aqueous extract once per week, and each aliquot was keptrefrigerated when not in use.

Another ophthalmological examination was conducted four weeks after thefirst administration of the extract. The vision in the both eyes hadimproved to 20/30, and upon visual inspection the cataracts appearednoticeably clearer. The remainder of the ophthalmological examinationwas within normal limits.

The patient reported that she could now read the newspaper again,something she hadn't been able to do for five years.

Based on the experimental results summarized above, it is believed thatthe present invention comprises treatment methods and compositions thatcan ameliorate the effects, and/or inhibit the development, of senilecataracts in an animal subject, for example, a dog, a cat, a horse, acow, a mouse, a rat or a human. As to human subjects in particular, itshould be understood that, when used propylactically, although anypatient in a demographic group at significant risk for senile cataractscan be treated (for example, humans over the age of 50), subjects canalso be selected using more specific criteria. For example, patients whohave biomicroscopic clinical evidence of an incipient senile cataract,or patients who have biomicroscopic evidence of a senile cataractcombined with a decrease in visual acuity, can be selected fortreatment.

The present invention is useful in the treatment and/or prophylaxis ofsenile cataracts, and therefore finds industrial applicability in humanand veterinary medicine.

While there has been described what are at present considered to be thepreferred embodiments of the present invention, it will be apparent tothose skilled in the art that the embodiments described herein are byway of illustration and not of limitation. Therefore, it is to beunderstood that various changes and modifications may be made in theembodiments disclosed herein without departing from the true spirit andscope of the present invention, as set forth in the appended claims.

1. A method for inhibiting or preventing the development of a senilecataract or inhibiting the progression of a senile cataract or anincipient senile cataract in a subject, the method comprising the stepof administering to a subject in need of such treatment atherapeutically effective amount of an extract of Capraria biflora,together with one or more therapeutically acceptable additives.
 2. Amethod in accordance with claim 1 wherein said extract is an aqueousextract and is prepared from at least one organ of said Capraria bifloraselected from the group consisting of the leaves, stems, stalks, twigs,flowers, roots and seeds.
 3. A method in accordance with claim 2 whereinsaid extract is prepared from the leaves of said Capraria biflora.
 4. Amethod in accordance with claim 1 wherein said extract is administeredtopically, systemically or intraocularly.
 5. A method in accordance withclaim 4 wherein said extract is administered topically to an afflictedeye of the subject in the form of liquid eye drops.
 6. A method inaccordance with claim 5 wherein said subject is a human being and saidextract is administered in an amount comprising substantially 0.15 mldaily, for a period of four to six weeks.
 7. A method in accordance withclaim 6 wherein said extract is an aqueous extract prepared from atleast one organ of said Capraria biflora selected from the groupconsisting of the leaves, stems, stalks, twigs, flowers, roots andseeds.